Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000521273 | SCV000621507 | uncertain significance | not provided | 2017-10-16 | criteria provided, single submitter | clinical testing | The R1010H variant in the SETX gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1010H variant is observed in 26/30718 (0.08%) alleles from individuals of South Asian background, in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). The R1010H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret R1010H as a variant of uncertain significance. |
Invitae | RCV001306845 | SCV001496229 | likely benign | Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2023-11-14 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV001662531 | SCV001880507 | likely benign | not specified | 2020-10-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002438262 | SCV002753421 | uncertain significance | Inborn genetic diseases | 2021-01-15 | criteria provided, single submitter | clinical testing | The p.R1010H variant (also known as c.3029G>A), located in coding exon 8 of the SETX gene, results from a G to A substitution at nucleotide position 3029. The arginine at codon 1010 is replaced by histidine, an amino acid with highly similar properties. This variant was detected in an amyotrophic lateral sclerosis (ALS) cohort; however, clinical details were limited (Zhang H et al. Amyotroph Lateral Scler Frontotemporal Degene, 2018 08;19:419-425). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant juvenile amyotrophic lateral sclerosis 4 (ALS4); however, its contribution to the development of autosomal recessive spinocerebellar ataxia with axonal neuropathy 2 (SCAN2) is uncertain. |